Displaying publications 301 - 320 of 392 in total

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  1. Increased level of activated gamma delta lymphocytes correlates with disease severity in HIV infection
    Norazmi MN, Arifin H, Jamaruddin MA
    Immunol Cell Biol, 1995 Jun;73(3):245-8.
    PMID: 7590898
    The lymphocyte subset expressing the gamma delta T cell receptor is increased in several infectious diseases including HIV infection. In this study the expression on gamma delta lymphocytes of the T cell activation markers CD25, HLA-DR and CD38, as well as the two isoforms of CD45, namely CD45RA and CD45RO, was determined in the peripheral blood of 56 HIV-infected intravenous drug users and 34 HIV-seronegative blood donors by two-colour flow cytometry. The percentage of gamma delta lymphocytes expressing HLA-DR and CD38 was higher than those in HIV-seronegative controls (P < 0.001 and P < 0.0001, respectively). Furthermore the HLA-DR+gamma delta+ lymphocytes correlated inversely with CD4+ T lymphocyte absolute count (P < 0.02 for both). The levels of gamma delta lymphocytes expressing CD25, CD45RA and CD45RO were similar to those in HIV-seronegative controls. Activated gamma delta lymphocytes may play a role in the HIV disease process and could provide a useful marker for disease progression.
    Matched MeSH terms: CD4-Positive T-Lymphocytes/metabolism*
  2. Fulltext Primary oesophageal Ki (CD30)-positive ALK+ anaplastic large cell lymphoma of T-cell phenotype
    Yaakup H, Sagap I, Fadilah SA
    Singapore Med J, 2008 Oct;49(10):e289-92.
    PMID: 18946602
    Primary oesophageal lymphoma is a very rare entity, with fewer than 30 reported cases worldwide. It represents an important cause of dysphagia. Most of the oesophageal lymphomas are diffuse large B-cell type, with only one reported case of anaplastic large cell lymphoma (ALCL) of T-cell phenotype. Primary oesophageal lymphomas that are not associated with an immunocompromised state tend to affect elderly patients. We describe the first case of primary oesophageal Ki (CD30)-positive ALK+ALCL of T-cell phenotype in a 34-year-old immunocompetent woman, who presented with a two-year history of dysphagia. She was treated with chemotherapy and endoscopic oesophageal dilations and stenting, resulting in complete remission of the lymphoma and resolution of the dysphagia. She then underwent autologous peripheral blood haematopoietic stem cell transplantation and remained disease-free two years after the diagnosis.
    Matched MeSH terms: T-Lymphocytes/metabolism
  3. Fulltext Occurrence of enteric parasitic infections among HIV-infected individuals and its relation to CD4 T-cell counts with a special emphasis on coccidian parasites at a tertiary care centre in South India
    Swathirajan CR, Vignesh R, Pradeep A, Solomon SS, Solomon S, Balakrishnan P
    Indian J Med Microbiol, 2017 Jan-Mar;35(1):37-40.
    PMID: 28303816 DOI: 10.4103/ijmm.IJMM_16_164
    CONTEXT: Diarrhoea is one of the major complications occurring in over 90% of HIV-infected individuals in developing countries. Coccidian group of parasites, being opportunistic pathogens, have been implicated as the most common causative agents of diarrhoea among HIV-infected population.

    AIMS: The aim was to study the magnitude of parasitic diarrhoea with special context to coccidian parasitic infections in HIV-infected individuals and their association with the patient's immunological status measured by CD4 T-cell counts.

    SETTINGS AND DESIGN: This investigation was performed between January 2002 and December 2014 at a tertiary HIV care centre in Chennai, South India.

    MATERIALS AND METHODS: Stool samples were collected and microscopically observed for parasites using direct, formal-ether-concentrated wet mounts and modified acid-fast staining for coccidian parasites. CD4 T-cell counts were done by FACScount.

    STATISTICAL ANALYSIS USED: All statistical analyses were performed using GraphPad Prism software, version 5.0, andP < 0.05 was considered statistically significant.

    RESULTS: Coccidian parasitic infection accounted for about 23.4% of parasitic infections, and of these, Cystoisospora belli was observed to be the most common cause of diarrhoea (88.8%), followed by Cryptosporidium spp. (9.9%) and Cyclospora spp. (1.3%). Trend analysis of coccidian aetiology during the study period revealed a significant rise in the positivity of C. belli and Cryptosporidium spp. (P = 0.001). Among the HIV patients with CD4+ T-cell counts <200 cells/μL, Cryptosporidium infection was most common (90%), followed by infection with C. belli(61.4%).

    CONCLUSIONS: Coccidian parasites continue to be the most common aetiological agent of diarrhoea among patients with HIV. The increasing trend of positivity of both cystoisosporiasis and cryptosporidiosis over the study period and the high positivity of cryptosporidiosis in patients with lower CD4+ T-cell counts are issues of serious concern. The findings call for the need for the early diagnosis of coccidian parasites and appropriate intervention among HIV-infected patients.
    Matched MeSH terms: CD4-Positive T-Lymphocytes/immunology*
  4. Fulltext Evaluation of the genotoxicity of zerumbone in cultured human peripheral blood lymphocytes
    Al-Zubairi AS, Abdul AB, Syam MM
    Toxicol In Vitro, 2010 Apr;24(3):707-12.
    PMID: 20123012 DOI: 10.1016/j.tiv.2010.01.011
    The chromosomal aberrations (CA) assay and micronucleus (MN) test were employed to investigate the effect in vitro of zerumbone (ZER) on human chromosomes. ZER is a sesquiterpene compound isolated from the rhizomes of wild ginger, Zingiber zerumbet Smith. The rhizomes of the plant are employed as a traditional medicine for some ailments and as condiments. ZER has been shown to have anti-cancer and apoptosis-inducing properties against various human tumour cells. It has also been shown to be active in vivo against a number of induced malignancies. Studies on ZER genotoxicity in cultured human peripheral blood lymphocytes (PBL) have not been reported so far. Therefore, the present study was undertaken to investigate the ability of ZER to induce chromosomal aberrations and micronuclei formation in human lymphocytes in vitro. Human blood samples were obtained from four healthy, non-smoking males aged 25-35years. Cultures were exposed to the drug for 48h at four final concentrations: 10, 20, 40 and 80 microM. Mitomycin C (MMC) was used as a positive control. The results of chromosomal aberrations assay showed that ZER was not clastogenic, when compared to untreated control, meanwhile MN test results showed a dose-dependent increase in MN formation. The overall clastogenic effect of ZER on human PBL was statistically not significant. In conclusion, ZER is a cytotoxic but not a clastogenic substance in human PBL.
    Matched MeSH terms: Lymphocytes/drug effects*
  5. Differential expression of immune-related genes in the bursa of Fabricius of two inbred chicken lines following infection with very virulent infectious bursal disease virus
    Mohd Isa F, Ahmed Al-Haj N, Mat Isa N, Ideris A, Powers C, Oladapo O, et al.
    Comp Immunol Microbiol Infect Dis, 2020 Feb;68:101399.
    PMID: 31837598 DOI: 10.1016/j.cimid.2019.101399
    Among different inbred chickens' lines, we previously showed that lines P and N of Institute for Animal Health, Compton, UK are the most susceptible and the least affected lines, respectively, following infection with very virulent infectious bursal disease virus (vvIBDV). In this study, the differential expressions of 29 different immune-related genes were characterized. Although, birds from both lines succumbed to infection, line P showed greater bursal lesion scores and higher viral copy numbers compared to line N. Interestingly, line N showed greater down-regulation of B cell related genes (BLNK, TNFSF13B and CD72) compared to line P. While up-regulation of T-cell related genes (CD86 and CTLA4) and Th1 associated cytokines (IFNG, IL2, IL12A and IL15) were documented in both lines, the expression levels of these genes were different in the two lines. Meanwhile, the expression of IFN-related genes IFNB, STAT1, and IRF10, but not IRF5, were up-regulated in both lines. The expression of pro-inflammatory cytokines (IL1B, IL6, IL18, and IL17) and chemokines (CXCLi2, CCL4, CCL5 and CCR5) were up-regulated in both lines with greater increase documented in line P compared to line N. Strikingly, the expression of IL12B was detected only in line P whilst the expression of IL15RA was detected only in line N. In conclusion, the bursal immunopathology of IBDV correlates more with expression of proinflammatory response related genes and does not related to expression of B-cell related genes.
    Matched MeSH terms: B-Lymphocytes/immunology
  6. Fulltext Complement opsonization of HIV affects primary infection of human colorectal mucosa and subsequent activation of T cells
    Bhattacharya P, Ellegård R, Khalid M, Svanberg C, Govender M, Keita ÅV, et al.
    Elife, 2020 Sep 02;9.
    PMID: 32876566 DOI: 10.7554/eLife.57869
    HIV transmission via genital and colorectal mucosa are the most common routes of dissemination. Here, we explored the effects of free and complement-opsonized HIV on colorectal tissue. Initially, there was higher antiviral responses in the free HIV compared to complement-opsonized virus. The mucosal transcriptional response at 24 hr revealed the involvement of activated T cells, which was mirrored in cellular responses observed at 96 hr in isolated mucosal T cells. Further, HIV exposure led to skewing of T cell phenotypes predominantly to inflammatory CD4+ T cells, that is Th17 and Th1Th17 subsets. Of note, HIV exposure created an environment that altered the CD8+ T cell phenotype, for example expression of regulatory factors, especially when the virions were opsonized with complement factors. Our findings suggest that HIV-opsonization alters the activation and signaling pathways in the colorectal mucosa, which promotes viral establishment by creating an environment that stimulates mucosal T cell activation and inflammatory Th cells.
    Matched MeSH terms: T-Lymphocytes/immunology
  7. Cross-reactive T-cell responses to the nonstructural regions of dengue viruses among dengue fever and dengue hemorrhagic fever patients in Malaysia
    Appanna R, Huat TL, See LL, Tan PL, Vadivelu J, Devi S
    Clin Vaccine Immunol, 2007 Aug;14(8):969-77.
    PMID: 17567768
    Dengue virus infections are a major cause of morbidity and mortality in tropical and subtropical areas in the world. Attempts to develop effective vaccines have been hampered by the lack of understanding of the pathogenesis of the disease and the absence of suitable experimental models for dengue viral infection. The magnitude of T-cell responses has been reported to correlate with dengue disease severity. Sixty Malaysian adults with dengue viral infections were investigated for their dengue virus-specific T-cell responses to 32 peptides antigens from the structural and nonstructural regions from a dengue virus isolate. Seventeen different peptides from the C, E, NS2B, NS3, NS4A, NS4B, and NS5 regions were found to evoke significant responses in a gamma interferon enzyme-linked immunospot (ELISPOT) assay of samples from 13 selected patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). NS3 and predominantly NS3(422-431) were found to be important T-cell targets. The highest peaks of T-cell responses observed were in responses to NS3(422-431) and NS5(563-571) in DHF patients. We also found almost a sevenfold increase in T-cell response in three DHF patients compared to three DF patient responses to peptide NS3(422-431). A large number of patients' T cells also responded to the NS2B(97-106) region. The ELISPOT analyses also revealed high frequencies of T cells that recognize both serotype-specific and cross-reactive dengue virus antigens in patients with DHF.
    Matched MeSH terms: T-Lymphocytes/immunology*
  8. Incidental Splenic Granuloma Due to Burkholderia pseudomallei: A Case of Asymptomatic Latent Melioidosis?
    Chow TK, Eu LC, Chin KF, Ong KC, Pailoor J, Vadivelu J, et al.
    Am J Trop Med Hyg, 2016 Mar 2;94(3):522-4.
    PMID: 26787155 DOI: 10.4269/ajtmh.15-0774
    We report a rare case of an asymptomatic latent melioidosis lesion in a posttraumatic splenectomy specimen from a diabetic patient. The 2-cm yellowish, lobulated lesion was found in the splenic parenchyma well away from the traumatized areas. Microscopically, it consisted of a central area of necrosis and exudate surrounded by macrophages, epithelioid cells, lymphocytes, and occasional multinucleated giant cells. Burkholderia bacilli were detected by a novel in situ hybridization (ISH) assay, and confirmed by polymerase chain reaction and sequencing to be Burkholderia pseudomallei. As melioidosis was not suspected initially, bacterial culture was not done but electron microscopy showed morphologically viable and dividing bacilli in the lesion. Moreover, the surgical wound became infected with B. pseudomallei several days post-surgery. After treatment with ceftazidime and trimethoprim/sulfamethoxazole, the wound infection cleared. We believe this could be a unique case of asymptomatic latent melioidosis in the spleen. In endemic countries, chronic granulomas should be investigated for B. pseudomallei infection, and if available, ISH may be helpful for diagnosis.
    Matched MeSH terms: Lymphocytes
  9. Fulltext Experimental exposure of Burkholderia pseudomallei crude culture filtrate upregulates PD-1 on T lymphocytes
    Menon N, Mariappan V, Vellasamy KM, Samudi C, See JX, Ganesh PS, et al.
    Access Microbiol, 2020;2(5):acmi000110.
    PMID: 32974575 DOI: 10.1099/acmi.0.000110
    Burkholderia pseudomallei is the causative agent for melioidosis. Because of its intracellular nature, the bacterium is capable of replicating within a plethora of eukaryotic cell lines. B. pseudomallei can remain dormant within host cells without symptoms for years, causing recrudescent infections. Here, we investigated the pathogenesis mechanism behind the suppression of T cell responses by B. pseudomallei . Peripheral blood mononuclear cells (1×106 cells/well) isolated by Ficoll Paque (Sigma-Aldrich) density gradient centrifugation were incubated with optimized concentrations of bacterial crude culture filtrate antigens (CFAs) (10 ug ml-1) and heat-killed bacteria [1 : 10 multiplicity of infection (m.o.i.)]. Following incubation, cells were investigated for surface expression of coinhibitory molecules by flow cytometry. We found that B. pseudomallei induced the upregulation of programmed death 1 (PD-1), a molecule responsible for T cell exhaustion, on T cells in vitro following exposure to crude CFAs of B. pseudomallei . This upregulation of PD-1 probably contributes to poor immune surveillance and disease pathogenesis.
    Matched MeSH terms: T-Lymphocytes
  10. Fulltext Estrogen Receptors in Nonfunctioning Pituitary Neuroendocrine Tumors: Review on Expression and Gonadotroph Functions
    Haydar Ali Tajuddin A, Kamaruddin N, Sukor N, Azizan EA, Omar AM
    J Endocr Soc, 2020 Dec 01;4(12):bvaa157.
    PMID: 33241169 DOI: 10.1210/jendso/bvaa157
    Estrogen (17β-estradiol or E2) is a crucial regulator of the synthesis and secretion of pituitary reproductive hormones luteinizing hormone, follicle-stimulating hormone, and prolactin. In this review, we summarize the role of estrogen receptors in nonfunctioning pituitary neuroendocrine tumors (NF-Pitnets), focusing on immunoexpression and gonadotroph cell proliferation and apoptosis. Gonadotroph tumors are the most common subtype of NF-Pitnets. Two major estrogen receptor (ER) isoforms expressed in the pituitary are estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). Overall, estrogen actions are mostly exerted through the ERα isoform on the pituitary. The G protein-coupled estrogen receptor (GPER) located at the plasma membrane may contribute to nongenomic effects of estrogen. Nuclear immunoreactivity for ERα and ERβ was highest among gonadotroph and null cell tumors. Silent corticotroph tumors are the least immunoreactive for both receptors. A significantly elevated ERα expression was observed in macroadenomas compared with microadenomas. ERα and ERβ may act in opposite directions to regulate the Slug-E-cadherin pathway and to affect invasiveness of NF-Pitnets. In the cellular pathway, ERs regulate estrogen-induced proliferation and differentiation and impact several signaling pathways including the MAPK and PI3K/Akt pathway. Estrogen was the first-discovered inducer of pituitary tumor transforming gene 1 that was abundantly expressed in NF-Pitnets. ERα can be a potential biomarker for predicting tumor size and invasiveness as well as therapeutic target for NF-Pitnets. Selective estrogen receptor modulators or antiestrogen may represent as an alternative choice for the treatment of NF-Pitnets.
    Matched MeSH terms: Lymphocytes, Null
  11. Eosinophilia and musculoskeletal disease
    Watts RA
    Curr Opin Rheumatol, 2001 Jan;13(1):57-61.
    PMID: 11148716
    Eosinophilia is occasionally a feature of rheumatic disease. The differential diagnosis of eosinophilia includes parasitic infection, systemic vasculitides, eosinophilic arthritis, and myopathies, together with the idiopathic hypereosinophilic syndrome and malignancy. Careful evaluation of the patient should enable an accurate diagnosis to be made. Parasitic infection is the commonest cause of eosinophilia worldwide and can cause systemic disease, as illustrated by the report of Sarcocystis myositis in a group of military personnel in Malaysia. A persistent arthropathy associated with eosinophilia, but not with parasitic infection, has been reported from the far East. Drugs may also cause eosinophilia, and there has recently been much discussion of the relation between Churg-Strauss syndrome and the leukotriene antagonist zafirlukast. The present view is that reduction of steroid dose allows unmasking of previously undiagnosed Churg-Strauss syndrome. The idiopathic hypereosinophilic syndrome may represent a lymphoproliferative process; evidence for this comes from the demonstration that many patients have a clonally expanded population of aberrant T cells.
    Matched MeSH terms: T-Lymphocytes
  12. Extranodal NK/T-cell lymphoma mimicking Crohn's colitis
    Wan Ahmad Kammal WS, Mohd Rose I, Md Zin RR, Raja Ali RA, Masir N
    Malays J Pathol, 2019 Aug;41(2):195-199.
    PMID: 31427556
    INTRODUCTION: Extranodal NK/T cell lymphoma is a rare tumour, typically involving the upper aerodigestive tract. Even rarer is primary extranasal disease involving the skin, testis, soft tissue and gastrointestinal tract.

    CASE REPORT: We report a case of a 46-year-old Chinese male who presented with six months history of abdominal pain, weight loss and rectal bleeding. Diagnostic colonoscopy revealed multiple aphthous ulcers within the ileo-caecal region and distal transverse colon, separated by normal mucosa, mimicking skip lesions of Crohn's colitis. Computer topography (CT) scan of the abdomen showed multiple circumferential thickenings involving predominantly the right colon. A clinical diagnosis of colonic Crohn's disease with possible perforation was made. An extended right hemicolectomy was performed due to uncontrolled rectal bleeding. Histopathology examination of the colon showed infiltration by malignant lymphoid cells associated with necrosis, angiocentricity and angiodestruction. Immunohistochemical studies confirmed T-cell monoclonality, presence of cytotoxic granules and Epstein-Barr virus (EBV) infection. A diagnosis of extranodal NK/T cell lymphoma of the colon was made.

    DISCUSSION: These findings highlight that colonic NK/T cell lymphoma may clinically mimic other benign inflammatory lesions and should be one of the differential diagnoses in patients presenting with gastrointestinal lesions. The final diagnosis is only possible with appropriate histological and immunohistochemical studies.

    Matched MeSH terms: T-Lymphocytes
  13. Fulltext Optic nerve infiltration in adult acute lymphoblastic leukaemia (ALL)
    Muhamad-Amin, R., Nur Hasnida Gani, Liza-Sharmini, A.T., Zamli, A.H.
    Journal of Biomedical and Clinical Sciences, 2018;3(2):22-25.
    MyJurnal
    Acute lymphoblastic leukemia (ALL) is the most common
    childhood leukaemia. It is a malignant neoplasm caused by the proliferation of
    poorly differentiated precursors of the lymphoid cells. It is relatively
    uncommon in adult. In adult ALL, central nervous system (CNS) involvement
    is associated with poor prognosis. The incidence of CNS involvement has
    been reported between 7% and 15 %. We report a case of optic nerve
    infiltration in ALL in a 49 years old gentleman. He was diagnosed with
    precursor-B ALL. He was treated with chemotherapy and CNS prophylactic
    regime. He presented with sudden left eye loss of vision for one-day duration
    with history of right eye inferior visual field loss for the past three months. His
    visual acuity was no perception to light on the left eye and 6/9 on the right
    eye. There was marked left relative afferent pupillary defect. The right eye
    showed decreased in optic nerve function with inferior visual field defect.
    Anterior segment examination was unremarkable in both eyes. Left optic disc
    appeared normal but the right optic disc was pale. Blood investigation
    showed no sign of infection or haemoconcentration. Cerebral spinal fluids
    examination revealed abundant of white cells and blast cells. Magnetic
    resonant imaging showed bilateral optic nerve enhancement suggesting of
    bilateral optic nerves infiltration. He was started on a new regime of
    chemotherapy followed by cranial radiotherapy. Unfortunately, he succumbed
    to death due to septicaemia. There are variations in clinical presentation of
    optic nerve infiltration in leukaemic patients. Normal appearance of optic disc
    may not exclude the possibility of infiltration by malignancy. Assessment of
    the optic nerve function and imaging is helpful for the detection of leukaemic
    infiltration. Early detection of optic nerve infiltration is important for initiation or
    change of therapy to prevent mortality.
    Matched MeSH terms: Lymphocytes
  14. Fulltext K-Ras Peptide Mimotope Induces Antigen Specific Th1 and B-Cell Immune Responses against G12A-Mutated K-Ras Antigen in Balb/c Mice
    Siak PY, Wong KY, Song AA, Rahim RA, In LLA
    Vaccines (Basel), 2021 Feb 26;9(3).
    PMID: 33652552 DOI: 10.3390/vaccines9030195
    KRAS G12A somatic point mutation in adenocarcinomas is categorized clinically as ineligibility criteria for anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapies. In this study, a modified G12A-K-ras epitope (139A) with sequence-specific modifications to improve immunogenicity was developed as a potential vaccine against G12A-mutant KRAS cancers. Additionally, coupling of the 139A epitope with a tetanus toxoid (TTD) universal T-cell epitope to improve antigenicity was also reported. To facilitate convenient oral administration, Lactococcus lactis, which possesses innate immunomodulatory properties, was chosen as a live gastrointestinal delivery vehicle. Recombinant L. lactis strains secreting a G12A mutated K-ras control and 139A with and without TTD fusion were generated for comparative immunogenicity assessment. BALB/c mice were immunized orally, and high survivability of L. lactis passage through the gastrointestinal tract was observed. Elevations in B-cell count with a concomitant titre of antigen-specific IgG and interferon-γ secreting T-cells were observed in the 139A treated mice group. Interestingly, an even higher antigen-specific IgA response and interferon-γ secreting T-cell counts were observed in 139A-TTD mice group upon re-stimulation with the G12A mutated K-ras antigen. Collectively, these results indicated that an antigen-specific immune response was successfully stimulated by 139A-TTD vaccine, and a TTD fusion was successful in further enhancing the immune responses.
    Matched MeSH terms: T-Lymphocytes
  15. Extracellular Vesicles Derived From Colorectal Cancer Affects CD8 T Cells: An Analysis Based on Body Mass Index
    Abu N, Othman N, Ab Razak NS, Bakarurraini NAAR, Nasir SN, Soh JEC, et al.
    Front Cell Dev Biol, 2020;8:564648.
    PMID: 33324632 DOI: 10.3389/fcell.2020.564648
    Colorectal cancer (CRC) is one of the most widely diagnosed cancers worldwide. It has been shown that the body-mass index (BMI) of the patients could influence the tumor microenvironment, treatment response, and overall survival rates. Nevertheless, the mechanism on how BMI affects the tumorigenesis process, particularly the tumor microenvironment is still elusive. Herein, we postulate that extracellular vesicles (EVs) from CRC patients and non-CRC volunteers with different BMI could affect immune cells differently, in CD8 T cells particularly. We isolated the EVs from the archived serum of CRC patients with high and low BMI, as well as healthy controls with similar BMI status. The EVs were further characterized via electron microscopy, western blot and dynamic light scattering. Then, functional analysis was performed on CD8 T cells including apoptosis, cell proliferation, gene expression profiling and cytokine release upon co-incubation with the different EVs. Our results suggest that CRC-derived EVs were able to regulate the CD8 T cells. In some assays, low BMI EVs were functionally different than high BMI EVs. This study highlights the possible difference in the regulatory mechanism of cancer patients-derived EVs, especially on CD8 T cells.
    Matched MeSH terms: CD8-Positive T-Lymphocytes
  16. Fulltext A Synthetic Curcuminoid Analogue, 2,6-Bis-4-(Hydroxyl-3-Methoxybenzylidine)-Cyclohexanone (BHMC) Ameliorates Acute Airway Inflammation of Allergic Asthma in Ovalbumin-Sensitized Mice
    Tham CL, Yeoh SY, Ong CH, Harith HH, Israf DA
    Mediators Inflamm, 2021;2021:9725903.
    PMID: 33883974 DOI: 10.1155/2021/9725903
    2,6-Bis-(4-hydroxyl-3-methoxybenzylidine) cyclohexanone (BHMC), a synthetic curcuminoid analogue, has been shown to exhibit anti-inflammatory properties in cellular models of inflammation and improve the survival of mice from lethal sepsis. We further evaluated the therapeutic effect of BHMC on acute airway inflammation in a mouse model of allergic asthma. Mice were sensitized and challenged with ovalbumin (OVA), followed by intraperitoneal administration of 0.1, 1, and 10 mg/kg of BHMC. Bronchoalveolar lavage fluid, blood, and lung samples were collected, and the respiratory function was measured. OVA sensitization and challenge increased airway hyperresponsiveness (AHR) and pulmonary inflammation. All three doses of BHMC (0.1-10 mg/kg) significantly reduced the number of eosinophils, lymphocytes, macrophages, and neutrophils, as well as the levels of Th2 cytokines (IL-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF) as compared to OVA-challenged mice. However, serum level of IgE was not affected. All three doses of BHMC (0.1-10 mg/kg) were effective in suppressing the infiltration of inflammatory cells at the peribronchial and perivascular regions, with the greatest effect observed at 1 mg/kg which was comparable to dexamethasone. Goblet cell hyperplasia was inhibited by 1 and 10 mg/kg of BHMC, while the lowest dose (0.1 mg/kg) had no significant inhibitory effect. These findings demonstrate that BHMC, a synthetic nonsteroidal small molecule, ameliorates acute airway inflammation associated with allergic asthma, primarily by suppressing the release of inflammatory mediators and goblet cell hyperplasia to a lesser extent in acute airway inflammation of allergic asthma.
    Matched MeSH terms: Lymphocytes
  17. Fulltext Monitoring T Cells Responses Mounted by Therapeutic Cancer Vaccines
    Lim KP, Zainal NS
    Front Mol Biosci, 2021;8:623475.
    PMID: 33937323 DOI: 10.3389/fmolb.2021.623475
    With the regulatory approval of Provenge and Talimogene laherparepvec (T-VEC) for the treatment of metastatic prostate cancer and advanced melanoma respectively, and other promising clinical trials outcomes, cancer vaccine is gaining prominence as a cancer therapeutic agent. Cancer vaccine works to induce T cell priming, expansion, and infiltration resulting in antigen-specific cytotoxicity. Such an approach that can drive cytotoxicity within the tumor could complement the success of checkpoint inhibitors as tumors shown to have high immune cell infiltration are those that would respond well to these antibodies. With the advancements in cancer vaccine, methods to monitor and understand how cancer vaccines modify the immune milieu is under rapid development. This includes using ELISpot and intracellular staining to detect cytokine secretion by activated T cells; tetramer and CyTOF to quantitate the level of antigen specific T cells; proliferation and cell killing assay to detect the expansion of T cell and specific killing activity. More recently, T cell profiling has provided unprecedented detail on immune cell subsets and providing clues to the mechanism involved in immune activation. Here, we reviewed cancer vaccines currently in clinical trials and highlight available techniques in monitoring the clinical response in patients.
    Matched MeSH terms: T-Lymphocytes
  18. Chronic non-healing ulcers as presenting sign of acquired immunodeficiency syndrome
    Nasiri S, Barat T, Bidari-Zerehpoosh F, Mozafari N
    Malays Fam Physician, 2020;15(2):30-33.
    PMID: 32843942
    Atypical forms of herpes simplex virus (HSV) infections, which indicate severe impairment of cellular immunity can be challenging to diagnose. In this paper, we report the case of an atypical HSV infection presenting as chronic nonhealing wounds, which are the first sign of HIV, in a 50-year-old female patient. The lesions had emerged as two large, chronic, and painful ulcerations on the left buttock and labia major 8 months prior. The skin biopsy revealed multinucleated keratinocytes with ground glass nuclei and intranuclear Cowdry type A viral inclusions. A serologic test for HIV-1 was positive. Her CD4+ T-cell count was 42/mm3. Clinicians should be familiar with the dermatologic manifestations of HIV, as they are occasionally key to correctly suspecting an underlying HIV infection, allowing for early diagnosis and treatment.
    Matched MeSH terms: CD4-Positive T-Lymphocytes
  19. DNMT1 is associated with cell cycle and DNA replication gene sets in diffuse large B-cell lymphoma
    Loo SK, Ab Hamid SS, Musa M, Wong KK
    Pathol Res Pract, 2018 Jan;214(1):134-143.
    PMID: 29137822 DOI: 10.1016/j.prp.2017.10.005
    Dysregulation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) is associated with the pathogenesis of various types of cancer. It has been previously shown that DNMT1 is frequently expressed in diffuse large B-cell lymphoma (DLBCL), however its functions remain to be elucidated in the disease. In this study, we gene expression profiled (GEP) shRNA targeting DNMT1(shDNMT1)-treated germinal center B-cell-like DLBCL (GCB-DLBCL)-derived cell line (i.e. HT) compared with non-silencing shRNA (control shRNA)-treated HT cells. Independent gene set enrichment analysis (GSEA) performed using GEPs of shRNA-treated HT cells and primary GCB-DLBCL cases derived from two publicly-available datasets (i.e. GSE10846 and GSE31312) produced three separate lists of enriched gene sets for each gene sets collection from Molecular Signatures Database (MSigDB). Subsequent Venn analysis identified 268, 145 and six consensus gene sets from analyzing gene sets in C2 collection (curated gene sets), C5 sub-collection [gene sets from gene ontology (GO) biological process ontology] and Hallmark collection, respectively to be enriched in positive correlation with DNMT1 expression profiles in shRNA-treated HT cells, GSE10846 and GSE31312 datasets [false discovery rate (FDR) <0.05]. Cell cycle progression and DNA replication were among the significantly enriched biological processes (FDR <0.05). Expression of genes involved in the activation of cell cycle and DNA replication (e.g. CDK1, CCNA2, E2F2, PCNA, RFC5 and POLD3) were highly correlated (r>0.8) with DNMT1 expression and significantly downregulated (log fold-change
    Matched MeSH terms: B-Lymphocytes
  20. Fulltext Clinical and demographic pattern of chronic granulomatous disease (CGD) from a multicenter perspective: Malaysia's experience over 26 years
    Noh LM, Latiff AHA, Ismail IH, Noah RM, Wahab AA, Hamid IJA, et al.
    Allergy Asthma Clin Immunol, 2021 May 17;17(1):50.
    PMID: 34001231 DOI: 10.1186/s13223-021-00551-4
    BACKGROUND: A retrospective review of clinical manifestations and demographic pattern of patients diagnosed as chronic granulomatous disease (CGD) from 7 hospitals in Malaysia. An analysis of the available database would establish clinical characteristics, diagnoses and outcome including microbiologic pattern. Studying the demography allows us to document the occurrence of CGD amongst multiethnic groups and its geographical distribution for Malaysia.

    METHODS: Data from the Malaysia Primary Immunodeficiency Network (MyPIN) with cases of CGD diagnosed from 1991 until 2016 were collated and analysed.

    RESULTS: Twenty patients were diagnosed as CGD. Males (N = 13, 65%) outnumber females (N = 7, 35%). CGD is commonest amongst the Malays (65%) followed by the Chinese (15.0%), Indians (10.0%) and natives of Borneo (10.0%), reflecting the ethnic composition of the country. The mean age of diagnosis was 3.7 years. There was a positive family history in 40% of the cases. Abscess was the main presenting feature in 16 patients (80%) with one involving the brain. Pneumonia occurred in 10 (50%) and one with complicated bronchiectasis. Catalase-positive bacteria were the most commonly isolated pathogen with Chromobacterium violaceum predominating (N = 5, 25%) with consequent high mortality (N = 4, 80%). All CGD patients with C. violaceum infection displayed CD4 + (T helper cells) lymphopenia.

    CONCLUSION: This study has shown CGD occurs in the major ethnic groups of Malaysia. To the best of our knowledge, this is the first and the largest series of chronic granulomatous disease in South East Asia which may be reflective of similar clinical pattern in the region. C. violaceum infection is associated with a higher mortality in CGD patients in Malaysia. All the CGD patients with C. violaceum infection in this patient series displayed CD4 + (T helper) lymphopenia. We recorded rare clinical manifestation of CGD viz. brain abscess and bronchiectasis.

    Matched MeSH terms: T-Lymphocytes, Helper-Inducer
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